The progress that we made during the initial funding period (The Hippocampus and Relational (Declarative) Memory) has had a tremendous impact on the field of memory research in general, and it is now widely accepted that relational memory is a primary function of the hippocampus. This renewal application seeks to discover how the hippocampus, a brain structure unequivocally necessary for feats of long-term memory, plays a crucial role in the construction and use of memory in real-time. Because hippocampal pathology has been implicated in many brain disorders, including amnesia, schizophrenia, Alzheimer's disease and the autism spectrum, our efforts to extend the functional description of the hippocampus beyond the traditional purview of long-term memory are necessary for understanding the pathological mechanisms of these diseases and for developing accurate assays for their diagnosis and treatment. The proposed studies build upon the strides we have made during the initial award period in showing how the hippocampus participates in expressions of memory that occur on very short timescales (i.e., seconds). The current studies will push further, and will seek to determine the role of the hippocampus in truly on-line memory processing, with no "retention delay." Furthermore, we will show how the hippocampus is directly and immediately linked to various behavioral expressions of memory;that is, how the moment-to-moment ramifications of hippocampal processing are used to control in real-time our interactions with the information in the environment. Our studies will employ sophisticated behavioral methods, such as eye-tracking, in conjunction with both functional neuroimaging studies in healthy individuals and with neuropsychological studies of amnesic patients with circumscribed hippocampal damage. We will therefore be uniquely able to determine both how the hippocampus normally interacts with the rest of the brain during on-line processing, and how these transactions are disrupted when the functional integrity of the hippocampus is compromised. Studying hippocampal processing at this network/systems level is directly relevant to understanding neuropathological disorders, which are widely characterized as disrupting brain function at a network level. PUBLIC HEALTH RELEVANCE: A host of prevalent, debilitating, and costly neuropathological disorders involve disorganized interactions between the hippocampus and the rest of the brain. We will unravel this process by describing how the hippocampus normally interacts with other brain structures during ongoing behavior (i.e., in real-time), and will show what happens when the hippocampus is disrupted by brain lesions. Our findings will therefore be directly relevant to understanding, diagnosing, and treating these disorders.